Evidence map›Paper›PMID 38168984›Full record

ArticleNature biotechnology2024

Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion.

Jonathan C Schmok, Manya Jain, Lena A Street, Alex T Tankka, Danielle Schafer, Hsuan-Lin Her, Sara Elmsaouri, Maya L Gosztyla, Evan A Boyle, Pratibha Jagannatha and 4 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Nature biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
7.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. RNA-binding proteins connect Exon usage to the chromatin.NAR genomics and bioinformatics · 2025
    Article
  9. Article
  10. Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Strategies for programmable manipulation of alternative splicing.Current opinion in genetics & development · 2024
    Review
  16. Precision Transcriptome Editing.ACS synthetic biology · 2024
    Review
  17. Article
  18. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Jonathan C SchmokDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-5173-902X
Manya JainDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Lena A StreetDepartment of Biological Sciences, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0002-5473-6713
Alex T TankkaDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Danielle SchaferDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Hsuan-Lin HerDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Sara ElmsaouriDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Maya L GosztylaDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4758-4800
Evan A BoyleDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Pratibha JagannathaDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
En-Ching LuoDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Ester J KwonDepartment of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Marko JovanovicDepartment of Biological Sciences, Columbia University, New York, NY, USA.
Gene W YeoDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. geneyeo@ucsd.edu.ORCID http://orcid.org/0000-0002-0799-6037
University of California San Diego · USColumbia University · US

Funding

TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2012 to 2024
$17.3M
Functional RNA elements in the human genomeR01HG004659 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kevin Daniel Corbett, Eugene Wei-Ming Yeo · 2008 to 2026
$12.4M
Using Networks to Seed Hierarchical Whole-cell Models of CancerU54CA209891 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI IDEKER, TREY · 2017 to 2021
$10.9M
Predoctoral and Postdoctoral Training in Cancer Cell BiologyT32CA067754 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEAN Y.J. WANG · 1995 to 2026
$6.5M
A comprehensive binding and functional map of human RNA-binding proteinsU24HG009889 · NHGRI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI GRAVELEY, BRENTON R., YEO, EUGENE WEI-MING · 2022 to 2025
$5.5M
Extensive multiplexing of protein nucleic-acid interactions to comprehensively study gene expression regulation from chromatin to mRNA degradationR01HG012216 · NHGRI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI GUTTMAN, MITCHELL, JOVANOVIC, MARKO · 2022 to 2025
$3.1M
Defining the programmed proteome rejuvenation underlying gametogenesisR01AG071869 · NIA · UNIVERSITY OF CALIFORNIA BERKELEY · PI BRAR, GLORIA ANN, JOVANOVIC, MARKO · 2021 to 2025
$2.9M
Regulation of Protein Production Dynamics:RNA Binding Proteins and the Ribosome CodeR35GM128802 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI JOVANOVIC, MARKO · 2018 to 2022
$2.3M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada) PGS D-532649-2019National Science Foundation (NSF) 2224211National Science Foundation (NSF) DGE-2038238NCI NIH HHS T32 CA067754NCI NIH HHS U54 CA209891NHGRI NIH HHS R01 HG004659NHGRI NIH HHS R01 HG012216NHGRI NIH HHS U24 HG009889NIA NIH HHS R01 AG071869NIGMS NIH HHS P41 GM103504NIGMS NIH HHS R35 GM128802NIH HHS S10 OD026929U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01AG071869U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HG012216U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35GM128802U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32CA067754
6 · The paper itself

Abstract

RNA-binding proteins (RBPs) modulate alternative splicing outcomes to determine isoform expression and cellular survival. To identify RBPs that directly drive alternative exon inclusion, we developed tethered function luciferase-based splicing reporters that provide rapid, scalable and robust readouts of exon inclusion changes and used these to evaluate 718 human RBPs. We performed enhanced cross-linking immunoprecipitation, RNA sequencing and affinity purification-mass spectrometry to investigate a subset of candidates with no prior association with splicing. Integrative analysis of these assays indicates surprising roles for TRNAU1AP, SCAF8 and RTCA in the modulation of hundreds of endogenous splicing events. We also leveraged our tethering assays and top candidates to identify potent and compact exon inclusion activation domains for splicing modulation applications. Using these identified domains, we engineered programmable fusion proteins that outperform current artificial splicing factors at manipulating inclusion of reporter and endogenous exons. This tethering approach characterizes the ability of RBPs to induce exon inclusion and yields new molecular parts for programmable splicing control.

Indexed as

Alternative SplicingExonsRNA-Binding ProteinsHEK293 CellsHumansRNA-Binding Proteins

Identifiers

PMID38168984
PMCPMC11389820
OpenAlexW4390507485

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.